Impact of cerebrospinal fluid matrix or the detection of Alzheimer's disease with Aβ42 and influence of disease on the total-Aβ42/Aβ40 ratio.

The 42-amino acid fragment of amyloid beta (A beta 1-42) in cerebrospinal fluid has continued to be important for detecting cerebral p-amyloidosis in Alzheimer's disease (AD). However, there are impediments to our ability to fully understand this measurement, including matrix interference and changes linked to apolipoprotein E (APOE) epsilon 4 genotype. This study investigated matrix interference as a contributing factor for detecting AD in APOE E epsilon-negative patients by comparing total extractable A beta 1-42 to free A1 beta-42. It also examined the ratio of total A beta 1-42 to A beta 1-40, since changes relative to other A beta peptides may provide a measurement of cerebral p-amyloidosis that is neutral to changes in APP metabolism. Total A beta-42 lost the diagnostic power for detecting AD, confirming a role for matrix in the diagnostic. However, when total A1 beta 1-42/A beta 1-40 was examined, the separation between groups was reestablished. This result was confirmed in a second sample set of unknown APOE status. These results confirmed that matrix interference in some cerebrospinal fluid samples appears to contribute to identifying AD patients and this can be compensated by using a total extracted A beta 1-42/A beta 1-40 ratio when matrix interference is small. It may be preferable to employ a total A beta 1-42/A beta 1-40 measurement, since this could minimize variability because of matrix and compensate for across patient differences.